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首页> 美国卫生研究院文献>Pharmaceutics >Preparation Characterization and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl
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Preparation Characterization and In Vivo Pharmacokinetic Evaluation of Polyvinyl Alcohol and Polyvinyl Pyrrolidone Blended Hydrogels for Transdermal Delivery of Donepezil HCl

机译：聚乙烯醇和聚乙烯吡咯烷酮共混水凝胶用于盐酸多奈哌齐的透皮递送的制备表征和体内药代动力学评价

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Transdermal delivery systems are emerging platforms for the delivery of donepezil hydrochloride (DH) for treating Alzheimer’s disease. The primary aim of this study was to develop polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogels and to evaluate their feasibility for delivering DH via a transdermal route. Physicochemical properties, such as gel fraction (%), swelling ratio (%), weight loss (%), mechanical strength, elongation at break, and Young’s modulus of the prepared hydrogels were evaluated. Furthermore, in vitro skin permeation and in vivo pharmacokinetic studies were performed. With an increased concentration of propylene glycol (PG), the gel fraction (%), maximum strength, and elongation at break decreased. However, the swelling ratio (%) and weight loss (%) of hydrogels increased with increased PG content. The 26% PG-hydrogel was superior, with an enhancement ratio of 12.9 (*** < 0.001). In addition, the 11% PG-hydrogel and 1% PG-hydrogel exhibited an enhancement ratio 6.30-fold (*** < 0.001) and 2.85-fold (* < 0.05) higher than that exhibited by control, respectively, indicating a promising effect of PG on skin permeation. In addition, in vivo pharmacokinetic studies on hairless rats assessed the expediency for transdermal delivery of DH. The transdermal delivery of optimized hydrogel-patches with two different doses of DH revealed that the maximum plasma concentration and area under the curve were dose dependent, and the time to reach the maximum concentration was 8 h. Thus, optimized hydrogels have the potential to enhance the transdermal delivery of DH and could be a novel clinical approach.
机译：透皮给药系统是用于治疗盐酸多奈哌齐（DH）的新型平台，可用于治疗阿尔茨海默氏病。这项研究的主要目的是开发聚乙烯醇和聚乙烯吡咯烷酮混合水凝胶，并评估它们通过透皮途径递送DH的可行性。评价了所制备的水凝胶的理化性质，例如凝胶分数（％），溶胀率（％），重量损失（％），机械强度，断裂伸长率和杨氏模量。此外，进行了体外皮肤渗透和体内药代动力学研究。随着丙二醇（PG）浓度的增加，凝胶分数（％），最大强度和断裂伸长率降低。然而，水凝胶的溶胀率（％）和重量损失（％）随着PG含量的增加而增加。 26％PG-水凝胶性能更佳，增强率为12.9（*** <0.001）。此外，11％PG-水凝胶和1％PG-水凝胶分别显示出比对照高6.30倍（*** <0.001）和2.85倍（* <0.05）的增强率，这表明有希望PG对皮肤渗透的影响。另外，对无毛大鼠的体内药代动力学研究评估了DH透皮递送的便利性。优化水凝胶贴剂的两种不同剂量的DH透皮给药显示最大血浆浓度和曲线下面积是剂量依赖性的，达到最大浓度的时间为8小时。因此，优化的水凝胶具有增强DH透皮递送的潜力，并且可能是一种新颖的临床方法。

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